This project is concerned with the molecular interactions governing transport across red cell membranes; we are studying four aspects of the problem: 1. In an attempt to understand the relations between cardiac glycosides and the transport receptor complex on the cell surface, studies are in progress to see whether different receptor sites are involved in anchoring the glycoside and in inhibiting cation transport. 2. Depletion of red cell membrane cholesterol inhibits both ouabain sensitive and total K influx. We plan to extend these studies to other perturbations of membrane lipids by using phospholipases to cleave the membrane phopholipids selectively and studying the effect on K transport. 3. In studies on Na transport on dog red cells it has been found that a 10% decrease in cell volume increases Na influx threefold. Our studies indicate that phosphoglycerate kinase is the enzyme which links the volume effect to red cell metabolism. 4. Measurements have been made of the permeability of spherical lecithin bilayers to the homologous monoamides from formamide through valeramide. Rather than increasing monotonically with lipid solubility as predicted by Overton's rule, the permeability coefficients exhibit a minimum at acetamide. This has been ascribed to a combination of two processes: entrance into the membrane increasing with lipid solubility and diffusion through the membrane decreasing with the size of the permeating solute.